Drug‐related problems among hospitalized hypertensive and heart failure patients and physician acceptance of pharmacists' interventions at a teaching hospital in Ghana

Abstract Background Hypertensive and heart failure patients frequently require multiple drug therapy which may be associated with drug‐related problems (DRPs). Aim To determine the frequency, types, and predictors of DRPs, and acceptance of pharmacists' interventions among hospitalized hypertensive and heart failure patients. Method It was a prospective cross‐sectional study at the internal medicine department wards of Korle Bu Teaching Hospital (KBTH) between January and June 2019 using a validated form (the pharmaceutical care form used by clinical pharmacists at the medical department). DRPs were classified based on the Pharmaceutical Care Network Europe (PCNE) Classification scheme for DRPs V8.02. Descriptive and inferential statistics were used for data analysis. Results A total of 247 DRPs were identified in 134 patients. The mean number of DRPs was 1.84 (SD: 1.039) per patient. Most DRPs occurred during the prescribing process (40.5%; n(DRPs) = 100), and the highest prescribing problem was untreated indication (11.7%; n = 29). Other frequent DRPs were medication counseling need (25.1%; n = 62), administration errors 10.1%(n = 25), drug interaction (10.5%; n = 26), and “no” or inappropriate monitoring (10.5%; n = 26). The number of drugs received significantly predicted the number of DRPs (adjusted odds ratio [AOR]: 9.85; 95% CI: 2.04–47.50; p < 0.001). Clinical variables were significant predictors of number of DRPs (diabetic status: AOR: 0.41, 95% CI: 0.18–0.98, p < 0.05; statin use: AOR: 0.34, 95% CI: 0.14–0.81, p < 0.05; antiplatelet use: AOR: 5.95, 95% CI: 2.03–17.48, p < 0.01). Average acceptance of interventions by physicians was 71.6% (SD: 11.7). Most (70.6%; n = 48) accepted interventions were implemented by physicians (resolved). Conclusion DRPs frequently occur, with most problems identified in the prescribing process. Medication counseling was frequently needed. Patients' number of drugs and clinical factors predicted the occurrence of DRPs. Physicians accepted and implemented most interventions. Our findings suggest that clinical pharmacists have an important role in cardiovascular patient care, but this study should be replicated in other hospitals in Ghana to corroborate these findings.


| INTRODUCTION
Hypertension is increasingly becoming an important public health problem in Sub-Saharan Africa. [1][2][3] The disease is an important risk factor for heart failure, which is more prevalent in low socioeconomic settings and the Black population. [4][5][6][7] Hypertension is the predominant risk factor for heart failure in resource-limited settings such as Africa. 8 In Ghana, heart failure is a common reason for hospital attendance and admission among cardiovascular disease patients, and many heart failure patients present with hypertension which is a prevalent health problem in the country. 3,9,10 Treatment for hypertension and heart failure often requires the use of multiple cardiovascular drugs. 11,12 Medication use is potentially associated with problems (drug-related problems [DRPs]) that could affect treatment outcomes, especially when multiple pharmacological agents are required. The problems include medication errors and adverse drug reactions, and they can be classified with validated tools such as the Pharmaceutical Care Network Europe (PCNE), Cipolle's, and APS-Doc classification systems. [13][14][15] DRPs lead to substantial morbidity and mortality in addition to cost to health systems. DRPs reportedly caused over 218,000 deaths in the United States in 2000 alone. 16 The costs resulting from DRPs was estimated to be in excess of 177 billion U.S dollars in the same year. 16 DRPs have been associated with emergency department visits and hospitalization at internal medicine departments. 17,18 DRPs arise from prescribing, dispensing, and administration of medication. [19][20][21][22] The prevalence of DRPs in hospitalized patients varies [23][24][25] although several studies have shown a common occurrence. [25][26][27][28] Several studies have reported more than one DRP per patient. 25,[27][28][29][30] Studies have shown variations in DRPs between clinical departments. 25,26 A study in a tertiary care setting found DRPs to be more common in medical wards than other wards. Two studies showed an average DRP of 2.3 per patient in medical patients 25,31 while another study found a DRP rate of 1.4 in a tertiary hospital. 32 The definition of DRPs used by authors also accounts for variations in the reported rates of the problem. Compared with recent studies, an earlier review of DRPs assessing only medication errors found a lower rate of DRPs in hospitalized patients. 23 Although a review reported medication administration errors as the most prevalent DRPs, 23 other authors have reported different findings. Prescribing errors have also been reported as the most common DRPs, 20,27,28 while the occurrence of adverse drug reactions account for a variable proportion. 20,23,24 DRPs also vary among drugs, geography, and clinical departments/practice of hospitals. 33 Tigabu et al. concluded that DRPs are common on medical wards. 26 Although antibiotics have been found to be frequently implicated in DRPs, 20 cardiovascular drugs including blood pressure lowering medicines, statins, and antithrombotics have also shown a potential to frequently account for DRPs. 19,23,27,34 Furthermore, the number of drugs prescribed, demographic factors such as age and sex, drugs with a narrow therapeutic index, or renal elimination are likely to influence the frequency of DRPs. 19,23,25,34 Although DRPs are likely to occur in cardiovascular disease patients, 27,29,35 the frequency and type of DRPs are likely to vary depending on the method used to detect errors or ADRs (systematic screening of patients vs. chart review or spontaneous reporting) and the clinical departments or wards where studies are conducted. 23,25 The definitions or classification systems used by authors may also affect DRP findings. Preferable classifications systems for DRPs should have a clear definition, published validation, easy usability in practice, and grouped into main and subgroups (hierarchy of problems). 13 Despite DRPs being frequently reported, the majority can be prevented, especially through pharmaceutical care activities of pharmacists including monitoring, counseling, and interventions. 19,[23][24][25]36 Acceptance of pharmacists interventions by physicians in hospitalized patients vary although the majority of interventions may be accepted. 31,35,37,38 A retrospective study of DRPs in hospitalized patients found a rate of intervention acceptance by physicians in 71% of interventions made. 37 A prospective study reported intervention acceptance of more than 90% by physicians. 31 Some studies in hospitalized medical patients have, however, reported lower acceptance of pharmacists interventions. 35,38 Studies in cardiovascular patients have reported varying acceptance rates of pharmacists interventions with some studies reporting acceptance rates of half to two-thirds of interventions. 35,38 Most studies on DRPs were conducted in developed countries, leaving developing settings with the paucity of evidence. 20 In Ghana, evidence on DRPs published in peer-reviewed journals is very limited.
To the knowledge of the authors of this study, this is the first published research evaluating DRPs and their associated factors as well as intervention acceptance in hospitalized hypertensive and heart failure patients in Ghana using a systematic prospective design and the PCNE classification system. The aim of this study was to determine the frequency, types, and predictors of DRPs, and acceptance of pharmacists' interventions among hypertensive and heart failure patients admitted to the internal medicine wards of the

| Study settings
The study was conducted at the department of medicine of the

| Study participants
The study included hypertensive and heart failure patients admitted to medical wards of the main block of the medical department reviewed and identified by trained clinical pharmacists to have DRPs.

| Inclusion criteria
Patients admitted to the four (4) wards during the study period who were 18 years and above were included.

| Exclusion criteria
Patients admitted to the medical ICU; patients readmitted to the four wards whose 1st admission was within the study period and all those who were less than 18 years of age were excluded. Patients admitted to satellite wards such as fevers, chest, and stroke units were also excluded.

| Sample size calculation and sampling
Sample size for the study was calculated using open source epidermiologic statistics for public health (OpenEpi) for finite populations. 39 Our calculation was based on a study of cardiovascular admission trends in a tertiary hospital in Ghana over 12 years showing an average annual admission of 159 patients for heart failure with hypertension underlying most admissions. 9 We used a 39% prevalence of DRPs reported from a study of DRPs in hospitalized cardiovascular patients at a tertiary hospital. 35 The sample size was obtained using a Confidence level of 95% and confidence limit of 5% was 112. Using systematic sampling every 3rd heart failure and hypertensive patient who met the inclusion criteria was included. We included a total of 134 patients.
Study participants were recruited between January and June 2019.

| The PCNE classification system
The PCNE classification system is a validated tool for studying the nature, prevalence, and incidence of DRPs. 13 It is hierarchical. Unlike other classification systems, problems are separated from the causes (also called medication errors). The PCNE version V8.02 was used for this study. The basic classification has three primary domains for problems, eight primary domains for causes, and five primary domains for Interventions. The system includes classification for "Acceptance of the Intervention Proposals" On a more detailed level, there are seven grouped subdomains for problems, 35 for causes and 16 for interventions, and 10 for intervention acceptance. Subdomains explain the principal domains. It also has a scale to measure the extent of problem resolution. Consent was sought from patients whose cases were included in the study after data collectors explained the study to them. Definitions used for the various categories/types of DRPs in this study can be found in Supporting Information: Appendix 1.

| Data analysis
Data were analyzed using the statistical package for social scientist, SPSS version 22. Univariate, bivariate, and multivariate analysis were performed. Categorical variables were expressed as frequencies and percentages; while continuous variables were described using means and standard deviation. χ 2 tests were used to test the association between categorical variables. Logistic regression was used to determine the relationship between dependent and independent variables, and to determine the predictors of DRPs. p < 0.05 was considered statistically significant.

| Ethical approval
The study was approved by the institutional review board of the Korle Bu Teaching Hospital.

| Relationship between number of drugs, demographic, and clinical variables and number of DRPs
In a logistic regression analysis, the number of drugs received by patients significantly predicted the number of DRPs (   There were more patients with hypertension than heart failure. This reflects the high prevalence of hypertension in Ghana. 1,40 The total number of hypertensive and heart failure cases exceeded the total number of patients. This shows that some patients had concomitant hypertension and heart failure which reflects the frequent comorbidity of hypertension and heart failure in medical patients. 9 In this study, comorbidity was common and one-fifth of patients were diabetic. Studies

| Acceptance and implementation of pharmacists' interventions by physicians
show that diabetes is a risk factor for hypertension and heart failure and frequently coexists with these diseases. 9 Similar to our findings, DRPs have been reported to be common in tertiary hospitals in Africa. 27,30 Close to two DRPs were found per patient in our study. Studies in hypertensive and heart failure patients as well as those hospitalized for other cardiovascular conditions have also reported more than one DRP per patient. 27,29,31 Two studies in patients with cardiovascular disease reported two DRPs per patient. 29,31 Another study by Niriayo et al. in heart failure patients identified more than two DRPs per patient. 27 The high occurrence of DRPs suggests that the achievement of optimal outcomes in hypertensive and heart failure patients is threatened without the pharmaceutical care input of clinical pharmacists, and further suggests the critical need for clinical pharmacists on the medical wards.
DRPs occurred more frequently during the prescribing process.
This finding corroborates reports from several studies, including those in cardiovascular disease patients. 20 pharmacists interventions reduce all-cause mortality and hospitalization in heart failure. 55 A review of 36 studies in hospitalized patients evaluating pharmacists' participation in ward rounds, medication reconciliation, and drug-specific services also showed better treatment outcomes. 36 The review showed a reduction in medication errors and adverse drug events, as well as better medication adherence and shortened hospital stays. 36

| Limitations of the study
The study did not include patients on satellite wards and the intensive care unit of the medical department of the hospital. The relationship between renal and liver function and DRPs was not evaluated. The study was conducted at a single site. It may be challenging to extend the findings to other hospitals.

| CONCLUSION
DRPs frequently occur in hypertensive and heart failure patients with most problems identified in the prescribing process. Medication counseling for patients was frequently needed.